First-line sintilimab with pegaspargase, gemcitabine, and oxaliplatin in advanced extranodal natural killer/T cell lymphoma (SPIRIT): a multicentre, single-arm, phase 2 trial.

BACKGROUND: Programmed cell death protein 1 (PD-1) inhibitor sintilimab is effective in relapsed and refractory extranodal natural killer/T cell lymphoma (ENKTL), nasal type. We aimed to assess the safety and activity of sintilimab plus P-GEMOX (pegaspargase, gemcitabine, and oxaliplatin) in the first-line setting for advanced ENKTL. METHODS: The multicentre, single-arm, phase 2 trial was done at three medical centres in China. Patients aged 18-75 years with treatment-naive pathologically confirmed advanced ENKTL and an with Eastern Cooperative Oncology Group performance status score of 0-2 were eligible. Patients received intravenous sintilimab (200 mg on day 1), intramuscular pegaspargase (2000 U/m2 on day 1), intravenous gemcitabine (1 g/m2 on days 1 and 8), and intravenous oxaliplatin (130 mg/m2 on day 1) every 3 weeks for six cycles, followed by intravenous sintilimab (200 mg) every 3 weeks for up to 2 years or until disease progression or unacceptable toxicities. The primary endpoint was the complete response rate in the intention-to-treat population. The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), disease-free survival (DFS), and overall survival. This trial is registered with ClinicalTrials.gov, NCT04127227. Enrolment has been completed, and follow-up is ongoing. FINDINGS: Between Nov 29, 2019, and Sept 7, 2022, 34 eligible patients were enrolled (median age 39 years [IQR 32-55]; 25 [74%] of 34 patients were male; nine [26%] were female; and all were of Asian ethnicity). At the data cutoff (July 20, 2023), the median follow-up was 21 months (IQR 13-32). The complete response rate was 85% (29 of 34 patients, 95% CI 70-94). Five patients (15%; 95% CI 7-30) attained partial response and the ORR was 100% (34 of 34 patients). 24-month PFS was 64% (95% CI 48-86), 24-month DFS was 72% (54-95), and 36-month overall survival was 76% (52-100). The most common grade 3 or 4 treatment-related adverse events were neutropenia (17 [50%] of 34 patients), anaemia (10 [29%] patients), and hypertriglyceridemia (10 [29%] patients). Hypothyroidism was the most frequent immune-related adverse event (18 [53%]), including grade 3 hypothyroidism in one (3%) patient that caused treatment termination. No severe adverse events occurred. There were three deaths: one due to haemophagocytic syndrome, one due to disease progression, and one due to unknown cause, which were not considered to be treatment related. INTERPRETATION: Combination of sintilimab with P-GEMOX seems to be an active and safe first-line regimen for patients with advanced ENKTL. FUNDING: National Key Research and Development Program and National Natural Science Foundation of China, Guangzhou Science and Technology Program and the Clinical Oncology Foundation of Chinese Society of Clinical Oncology.

Effects of elevated CO2 concentration on cell structure and stress resistance physiology of Setaria italica under drought stress.

The frequency of drought will increase under further warming. The increase in atmospheric CO2 concentration, along with more frequent drought, will affect crop growth. We examined the changes of cell structure, photosynthetic physiology, antioxidant enzymes, osmotic regulatory substances, and yield of foxtail millet (Setaria ita-lica) leaves under different CO2 concentrations (ambient air CO2 concentration and ambient atmospheric CO2 concentration + 200 µmol·mol-1) and water treatment (soil moisture content maintained at 45%-55%, and 70%-80% of field capacity, representing mild drought and normal water condition, respectively). The results showed that elevated CO2 concentration increased the number of starch grains, the area of single starch grains, and the total area of starch grains in the chloroplast of millet mesophyll cells. Under mild drought condition, elevated CO2 concentration increased net photosynthetic rate of millet leaves at the booting stage by 37.9%, but did not affect water use efficiency at this stage. Elevated CO2 concentration increased net photosynthetic rate and water use efficiency of millet leaves under mild drought condition at the filling stage by 15.0% and 44.2%, respectively. Under mild drought condition, elevated CO2 concentration increased the content of peroxidase (POD) and soluble sugar in millet leaves at the booting stage by 39.3% and 8.0%, respectively, but decreased proline content by 31.5%. It increased the content of POD in millet leaves at the filling stage by 26.5% but decreased the content of MDA and proline by 37.2% and 39.3%, respectively. Under mild drought condition, elevated CO2 concentration significantly increased the number of grain spikes by 44.7% and yield by 52.3% in both years compared with normal water condition. The effect of elevated CO2 concentration on grain yield under mild drought conditions was higher than that under normal water condition. Under mild drought conditions, elevated CO2 concentration increased leaf thickness, vascular bundle sheath cross-sectional area, net photosynthetic rate, and water use efficiency of millet, improved the antioxidant oxidase activity, and changed the concentration of osmotic regulatory substances, alleviated the nega-tive effect of drought on foxtail millet, and finally increased the number of grains per ear and yield of foxtail millet. This study would provide a theoretical basis for millet production and sustainable agricultural development in arid areas under future climate change.

Phosphodiesterase type 10A inhibitor attenuates lung fibrosis by targeting myofibroblast activation.

Pulmonary fibrosis (PF) is a fatal and irreversible respiratory disease accompanied by excessive fibroblast activation. Previous studies have suggested that cAMP signaling pathway and cGMP-PKG signaling pathway are continuously down-regulated in lung fibrosis, whereas PDE10A has a specifically expression in fibroblasts/myofibroblasts in lung fibrosis. In this study, we demonstrated that overexpression of PDE10A induces myofibroblast differentiation, and papaverine, as a PDE10A inhibitor used for vasodilation, inhibits myofibroblast differentiation in human fibroblasts, Meanwhile, papaverine alleviated bleomycin-induced pulmonary fibrosis and amiodarone-induced oxidative stress, papaverine downregulated VASP/ß-catenin pathway to reduce the myofibroblast differentiation. Our results first demonstrated that papaverine inhibits TGFß1-induced myofibroblast differentiation and lung fibrosis by VASP/ß-catenin pathway.

[Applications of functional materials-based solid phase microextraction technique in forensic science].

Sample extraction is a crucial step in forensic analysis, especially when dealing with trace and ultra-trace levels of target analytes present in various complex matrices (e. g., soil, biological samples, and fire debris). Conventional sample preparation techniques include Soxhlet extraction and liquid-liquid extraction. However, these techniques are tedious, time-consuming, labor-intensive and require large amounts of solvents, which poses a threat to the environment and health of researchers. Moreover, sample loss and secondary pollution can easily occur during the preparation procedure. Conversely, the solid phase microextraction (SPME) technique either requires a small amount of solvent or no solvent at all. Its small and portable size, simple and fast operation, easy-to-realize automation, and other characteristics thus make it a widely used sample pretreatment technique. More attention was given to the preparation of SPME coatings by using various functional materials, as commercialized SPME devices used in early studies were expensive, fragile, and lacked selectivity. Examples of those functional materials include metal-organic frameworks, covalent organic frameworks, carbon-based materials, molecularly imprinted polymers, ionic liquids, and conducting polymers, all widely used in environmental monitoring, food analysis, and drug detection. However, these SPME coating materials have relatively few applications in forensics. Given the high potential of SPME technology for the in situ and efficient extraction of samples from crime scenes, this study briefly introduces functional coating materials and summarizes the applications of SPME coating materials for the analysis of explosives, ignitable liquids, illicit drugs, poisons, paints, and human odors. Compared to commercial coatings, functional material-based SPME coatings exhibit higher selectivity, sensitivity, and stability. These advantages are mainly achieved through the following approaches: First, the selectivity can be improved by increasing the π-π, hydrogen bonds, and hydrophilic/hydrophobic interactions between the materials and analytes. Second, the sensitivity can be improved by using porous materials or by increasing their porosity. Third, thermal, chemical, and mechanical stability can be improved by using robust materials or fixing the chemical bonding between the coating and substrate. In addition, composite materials with multiple advantages are gradually replacing the single materials. In terms of the substrate, the silica support was gradually replaced by the metal support. This study also outlines the existing shortcomings in forensic science analysis of functional material-based SPME techniques. First, the application of functional material-based SPME techniques in forensic science remains limited. On one hand, the analytes are narrow in scope. As far as explosive analysis is concerned, functional material-based SPME coatings are mainly applied to nitrobenzene explosives, while other categories, such as nitroamine and peroxides, are rarely or never involved. Research and development of coatings is insufficient and the application of COFs in forensic science has not yet been reported. Second, functional material-based SPME coatings have not been commercialized as they don't yet have inter-laboratory validation tests or established official standard analytical methods. Therefore, some suggestions are proposed for the future development of forensic science analyses of functional material-based SPME coatings. First, research and development of functional material-based SPME coatings, especially fiber coatings with broad-spectrum applicability and high sensitivity, or outstanding selectivity for some compounds, is still an important direction for SPME future research. Second, a theoretical calculation of the binding energy between the analyte and coating was introduced to guide the design of functional coatings and improve the screening efficiency of new coatings. Third, we expand its application in forensic science by expanding the number of analytes. Fourth, we focused on the promotion of functional material-based SPME coatings in conventional laboratories and established performance evaluation protocols for the commercialization of functional material-based SPME coatings. This study is expected to serve as a reference for peers engaged in related research.

Diagnostic performance and prognostic value of circulating tumor DNA methylation marker in extranodal natural killer/T cell lymphoma.

Circulating tumor DNA (ctDNA) carries tumor-specific genetic and epigenetic variations. To identify extranodal natural killer/T cell lymphoma (ENKTL)-specific methylation markers and establish a diagnostic and prognosis prediction model for ENKTL, we describe the ENKTL-specific ctDNA methylation patterns by analyzing the methylation profiles of ENKTL plasma samples. We construct a diagnostic prediction model based on ctDNA methylation markers with both high specificity and sensitivity and close relevance to tumor staging and therapeutic response. Subsequently, we built a prognostic prediction model showing excellent performance, and its predictive accuracy is significantly better than the Ann Arbor staging and prognostic index of natural killer lymphoma (PINK) risk system. Notably, we further establish a PINK-C risk grading system to select individualized treatment for patients with different prognostic risks. In conclusion, these results suggest that ctDNA methylation markers are of great value in diagnosis, monitoring, and prognosis, which might have implications for clinical decision-making of patients with ENKTL.

Diagnosing cervical lymph node metastasis in oral squamous cell carcinoma based on third-generation dual-source, dual-energy computed tomography.

OBJECTIVES: To investigate the potential of dual-energy computed tomography (DECT) parameters in identifying metastatic cervical lymph nodes in oral squamous cell carcinoma (OSCC) patients and to explore the relationships between DECT and pathological features. METHODS: Clinical and DECT data were collected from patients who underwent radical resection of OSCC and cervical lymph node dissection between November 2019 and June 2021. Microvascular density was assessed using the Weidner counting method. The electron density (ED) and effective atomic number (Zeff) in non - contrast phase and iodine concentration (IC), normalized IC, slope of the energy spectrum curve (λHU), and dual-energy index (DEI) in parenchymal phase were compared between metastatic and non - metastatic lymph nodes. Student's t-test, Pearson's rank correlation, and receiver operating characteristic curves were performed. RESULTS: The inclusion criteria were met in 399 lymph nodes from 103 patients. Metastatic nodes (n = 158) displayed significantly decreased ED, IC, normalized IC, λHU, and DEI values compared with non-metastatic nodes (n = 241) (all p < 0.01). Strong correlations were found between IC (r = 0.776), normalized IC (r = 0.779), λHU (r = 0.738), DEI (r = 0.734), and microvascular density. Area under the curve (AUC) for normalized IC performed the highest (0.875) in diagnosing metastatic nodes. When combined with the width of nodes, AUC increased to 0.918. CONCLUSION: DECT parameters IC, normalized IC, λHU, and DEI reflect pathologic changes in lymph nodes to a certain extent, and aid for detection of metastatic cervical lymph nodes from OSCC. KEY POINTS: • Electron density, iodine concentration, normalized iodine concentration, λHU, and dual-energy index values showed significant differences between metastatic and non-metastatic nodes. • Strong correlations were found between iodine concentration, normalized iodine concentration, slope of the spectral Hounsfield unit curve, dual-energy index, and microvascular density. • DECT qualitative parameters reflect the pathologic changes in lymph nodes to a certain extent, and aid for the detection of metastatic cervical lymph nodes from oral squamous cell carcinoma.

Newly found variations of the right posterior portal vein identified radiologically in 1,003 Chinese patients: a cross-sectional study.

Background: The anatomy of the right posterior portal vein (RPPV) plays an important role in planning hepatic resection, living transplantation and interventional radiological procedures, yet the incidence of variations of RPPV without a common trunk in Chinese persons is still unclear. Therefore, we conducted this study and discussed its clinical implications. Methods: A retrospective analysis of multidetector computed tomography (MDCT) scans was performed in 1,933 patients with various abdominal pathologies between September 28, 2018 through May 23, 2019. After excluding 930 patients, a total of 1,003 patients were included in this study. Variations of the RPPV without a common trunk were classified according to classification standards. Results: A total of 1,003 patients were included. RPPV without a common trunk was found in 216 (21.54%, 216/1,003) patients. Among them, we identified three variations of the origin from the right portal vein (RPV): first separate origin of P6, P7, or simultaneous separate origin of P6 and P7, and the incidences of these three variations were 1.50% (15/1,003), 6.58% (66/1,003) and 13.46% (135/1,003), respectively. Among 1,003 patients included in this study, 787 patients (78.46%, 787/1,003) showed that RPPV normally divided into P6 and P7 branches. Conclusions: Variations of the RPPV without a common trunk were not rare in Chinese population. Knowledge of this anatomic variation of the RPPV is extremely important for hepatic and transplant surgeons and interventional radiologists.

Vocal acoustic features may be objective biomarkers of negative symptoms in schizophrenia: A cross-sectional study.

BACKGROUND: There are currently no objective biomarkers that allow the quantification of negative symptoms of schizophrenia. This study therefore explored the use of acoustic features in identifying the severity of negative symptoms in patients with schizophrenia. METHODS: We recruited 79 inpatients who were diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (the schizophrenia group) at the Huilongguan Hospital in Beijing, China, and 79 healthy controls from the surrounding community (the control group). We assessed the clinical symptoms of the patients with schizophrenia using the Positive and Negative Syndrome Scale (PANSS) and the Brief Negative Symptom Scale (BNSS) and recorded the voice of each participant as they read emotionally positive, neutral, and negative texts. The Praat software was used to analyse and extract acoustic characteristics from the recordings, such as jitter, shimmer, and pitch. The acoustic differences between the two groups of participants and the relationship between acoustic characteristics and clinical symptoms in the patient group were analysed. RESULTS: There were significant differences between the schizophrenia and control groups in pitch, voice breaks, jitter, shimmer, and the mean harmonics-to-noise ratio (p < 0.05). Jitter was negatively correlated with the blunted affect and alogia subscale scores of the BNSS, both in the positive and neutral emotion conditions, but the correlation disappeared in the negative emotion condition. However, shimmer exhibited a stable negative correlation with the blunted affect and alogia subscale scores of the BNSS in all three emotion conditions. A linear regression analysis showed that pitch, jitter, shimmer, and age were statistically significant predictors of BNSS subscale scores. CONCLUSIONS: Acoustic emotional expression differs between patients with schizophrenia and healthy controls. Some acoustic characteristics are related to the severity of negative symptoms, regardless of semantic emotions, and may therefore be objective biomarkers of negative symptoms. A systematic method for assessing vocal acoustic characteristics could provide an accurate and feasible means of assessing negative symptoms in schizophrenia. TWEET: Acoustic emotional expression differs between patients with schizophrenia and healthy controls. A systematic method for assessing vocal acoustics could provide an accurate and feasible means of assessing negative symptoms in schizophrenia.

MiR-30e-3p inhibits gastric cancer development by negatively regulating THO complex 2 and PI3K/AKT/mTOR signaling.

BACKGROUND: Gastric cancer (GC) is a common type of digestive cancer with high morbidity and mortality rates worldwide. Considerable effort has been expended in understanding the mechanism of GC development and metastasis. The current study therefore explores the involvement of microRNAs in the regulation of GC progression. AIM: To explore the expression and function of miR-30e-3p in GC development. METHODS: MiR-30e-3p was found to be downregulated in GC, with low levels thereof predicting poor outcomes among patients with GC. Functionally, we revealed that miR-30e-3p suppressed cell growth and metastatic behaviors of GC cells. Bioinformatics analysis predicted that THO complex 2 (THOC2) was a direct target of miR-30e-3p, and the interaction between miR-30e-3p and THOC2 was further validated by a luciferase reporter assay. RESULTS: Our findings revealed that knockdown of THOC2 inhibited the growth and metastatic behaviors of GC cells. After investigating signaling pathways involved in miR-30e-3p regulation, we found that the miR-30e-3p/THOC2 axis regulated the PI3K/AKT/mTOR pathway in GC. CONCLUSION: Our findings suggest the novel functional axis miR-30e-3p/THOC2 is involved in GC development and progression. The miR-30e-3p/THOC2 axis could be utilized to develop new therapies against GC.

LncRNA GAS5 Suppresses Colorectal Cancer Progress by Target miR-21/LIFR Axis.

GAS5 is abnormally high in colorectal cancer tissues, which is a specific expression of lncRNA in colorectal cancer (CRC). Nevertheless, its biological function in CRC has not been elucidated. The abnormal high expression of GAS5 in CRC is the specific expression of lncRNA in CRC. The purpose of our study is to explore the effect of GAS5 on CRC and its mechanism. The expression of GAS5 in 53 paired normal and colorectal cancer tissues and colorectal cancer cell lines was detected by real-time PCR. The biological effects of GAS5, miR-21, and LIFR were measured by functional assays, including wound healing, transwell assays, and in vivo assays. We ensured the carcinogenesis role of GAS5 in CRC in the xenograft nude model. The dual-luciferase reporter assay system and chromatin immunoprecipitation method were used for target evaluation and Western blot for verification. GAS5 was significantly decreased in tumor tissues and CRC cells, and the low expression of CAS5 in CRC promoted tumor metastasis and decreased the survival of patients. GAS5 knockdown increases the cell viability, inhibits apoptosis, and promotes migration. Xenografted tumors in nude mice studies showed that GAS5 knockdown promoted tumor growth and caused worse lesions in colorectal. Furthermore, GAS5 increases the expression level of target gene LIFR to promote the apoptosis of CRC cells by binding to miR-21. Our study revealed that a novel pathway about lncRNA GAS5 inhibited the proliferation and metastasis of CRC cells by targeting miR-21/LIFR which provides a new strategy to treat CRC.

Establishment and Phenotypic Analysis of the Novel Gaucher Disease Mouse Model With the Partially Humanized Gba1 Gene and F213I Mutation.

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the GBA1 gene, which produces the glucocerebrosidase (GCase) protein. There are more than 500 mutations reported in GBA1, among which L444P (p.Leu444Pro) and F213I (p.Phe213Ile) are the most common in the Chinese population, while the function of F213I mutation remains elusive. This study aims to establish the GD mouse model of partially humanized Gba1 gene with F213I mutation. In vitro GCase activity assays showed that the product of partially humanized Gba1 gene, in which the mouse exons 5-7 were replace by the corresponding human exons, displayed similar activity with the wild-type mouse Gba1, while the F213I mutation in the humanized Gba1 led to significant decrease in enzyme activity. ES cell targeting was used to establish the mice expressing the partially humanized Gba1-F213I. Gba1 F213I/+ mice did not show obviously abnormal phenotypes, but homozygous Gba1 F213I/F213I mice died within 24 h after birth, whose epidermal stratum corneum were abnormal from the wild-type. The GCase activity in Gba1 F213I/F213I mice greatly decreased. In conclusion, our results showed that the partially humanized GD mouse model with the F213I mutation was developed and homozygous F213I mutation is lethal for newborn mice.

Interleukin-10 Attenuates Behavioral, Immune and Neurotrophin Changes Induced by Chronic Central Administration of Interleukin-1ß in Rats.

BACKGROUND: Activated microglia can trigger pro-inflammatory cytokine releases and neuroinflammation, which may inhibit astrocytes to produce neurotrophins and anti-inflammatory factors. Both eventually lead to neuron apoptosis or death. Furthermore, effective antidepressant or anti-dementia treatments can reduce pro-inflammatory cytokines, while enhance interleukin (IL)-10 production. However, the underline mechanism by which IL-10 modulates glial cell function, hence improves cognitive impairment or depression-like behavior is unknown. This study evaluated whether and how IL-10 attenuated chronic IL-1ß administration-induced behavioral changes and the possible involved mechanisms. METHODS: Rats received intracerebroventricular injection of IL-1ß and/or IL-10 for 14 days. Then animal memory and depression-like behavior, pro-inflammatory cytokines, glial activities, expression of brain-derived neurotrophic factor (BDNF), Trk B, p75, and apoptosis-related genes were studied. RESULTS: Compared to controls, significantly increased latent time and swimming distance in the Morris-water-maze, decreased sucrose consumption, and decreased locomotor and center zone entries in the open-field were found in rats administrated with IL-1ß. These changes were associated with the reduction of GFAP expression, and concentrations of BDNF and anti-inflammatory cytokine IL-10, but the increase in the expressions of CD11b, TrkB, p75, and Caspase-3, the ratio of Bax/Bcl-2, and the concentrations of IL-1ß, tumor necrosis factor-α, and IL-6. IL-10 treatment markedly attenuated IL-1ß-induced above changes, except for the expressions of neurotrophin receptors. CONCLUSION: IL-10-improved behavioral changes may be through suppressing microglia activity and inflammation, while restoring astrocyte function and BDNF expression.

A hydrostable CuII coordination network prepared hydrothermally as a "turn-on" fluorescent sensor for S2- and a selective adsorbent for methylene blue.

The effective monitoring of water pollution and further purification are pressing yet challenging issues for guaranteeing the health of human beings and the stabilization of ecological systems. For this purpose, the development of efficient sensing and adsorption materials as a result of supramolecular interactions, including coordination and H-bonding etc., have been attracting increasing attention. With the aid of a coordination-driven self-assembly strategy, a new nonporous 2D CuII coordination network, [Cu2L(H2O)2]n (donated as CuCP), based on H4L, where H4L = 4-(4-(3,5-di-carboxy-pyridin-4-yl)phenyl)pyridine-2,6-dicarboxylic acid, was afforded hydrothermally. Structural analysis indicated that CuCP featured a wrinkled network similar to the ancient Chinese folding screens and constructed by the fully deprotonated ligand L4- with the coordination mode of bis(µ2-η1:η1:η2) and penta-coordinated Cu2+, which could be further upgraded to a supramolecular 3D framework as a result of the synergism of multiple C-H⋯O hydrogen bonds. The hydrostability of CuCP could be maintained within a wide pH range from 2 to 12 as verified by PXRD determination, endowing it with potential environmental applications. Thanks to the combination of the soft Lewis acidity of Cu2+ and its large conjugated structure, CuCP could be used as a turn-on fluorescence sensor for S2- and exhibited a different fluorescence response when Na2S, (NH4)2S or H2S were incorporated, even in actual water samples. The sensing mechanisms were disclosed in detail by the combination of experiments and density functional theory (DFT) calculations. Furthermore, CuCP was shown to be a selective and recoverable adsorbent with a maximum adsorption capacity of 379 mg g-1 in 60 minutes for methylene blue (MB). The adsorption mechanism could be a combination of π⋯π stacking, n⋯π interaction, aggregation effects and Soft and Hard Acid-Base theory (HSAB). The results presented herein open up new perspectives for CuII species in environmental applications.

Anti-hyperglycaemic effect of labdane diterpenes isolated from the rhizome of Amomum maximum Roxb., an edible plant in Southwest China.

Amomum maximum Roxb. rhizome is a fork medicine mainly used in South and Southeast Asia. In present study, the hypoglycaemic effects of the ethanolic extract of A. maximum rhizome were demonstrated both on α-glucosidase assay in vitro and streptozotocin (STZ)-induced postprandial hyperglycaemia in mice. Furthermore, six labdane diterpenes, amoxanthin A (1), ottensinin (2), coronarin D (3), coronarin D methyl ether (4), isocoronarin D (5), and zerumin (6), were isolated from its ethyl acetate sub-fraction with the guidance of α-glucosidase inhibitory activity. Among these compounds, 2 and 6 exhibited significant inhibitory effect on α-glucosidase, as well as on STZ-induced high postprandial blood glucose levels in mice. Additionally, molecular docking analysis revealed that 2 and 6 could firmly bind to the active sites of α-glucosidase. These results suggest that compounds 2 and 6 are the main anti-hyperglycaemic agents present in A. maximum, which may demonstrate potential beneficial effects in diabetes management.

Clinical trait-connected network analysis reveals transcriptional markers of active psoriasis treatment with Liangxue-Jiedu decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is a complex recurrent inflammatory skin disease with different pathological changes in different stages. Psoriasis in its active stage, which is comparable to the blood-heat type in traditional Chinese medicine (TCM), has been treated by Liangxue Jiedu Decoction (LJD) in TCM for decades, with proven efficacy. According to TCM theories, LJD has the function of removing heat and pathogenic factors from the blood. AIM OF THE STUDY: We aimed to investigate the molecular features associated with the active stage psoriasis and identify genes responding to LJD treatment accompanied by lesion remission. MATERIALS AND METHODS: Healthy volunteers and psoriasis patients who met specific diagnostic criteria were recruited. Twenty-six transcriptomes were profiled from the peripheral blood mononuclear cells (PBMCs) of 10 psoriasis patients (pre- and post-treatment) and 6 healthy volunteers. RNA sequencing data were analyzed using an integrated approach combining differential gene expression analysis (DGEA) and weighted gene co-expression network analysis (WGCNA), by which gene expression was linked to multiple clinical traits, including psoriasis area and severity index (PASI), as well as the improvement rate of skin lesions (ΔPASI). The actions of LJD were then verified using an in vitro cell assay coupled to flow cytometric analysis and RT-PCR. RESULTS: We identified four network modules with statistical significance (P < 0.05), two of which connected to the PASI score, while the other two connected to 8-week treatment and ΔPASI, respectively. In psoriasis patients, activated inflammatory pathways and inhibited G-protein signaling genes (GTPase IMAP family member and G protein-coupled receptor) co-occurred, with high expression of CD83 and CD69, and low expression of CD160 and CD180, compared with the health. Accompanying LJD treatment and lesion remission, the expression of CD69 and cell cycle-related genes, including CCNA2, CCNB2, CDK1, and TOP2A, was down-regulated. The inhibitory role of LJD on CD69 expression was confirmed by the decline of activating naïve CD4+ T lymphocytes. CONCLUSION: Our study suggests that active psoriasis is characterized by unbalanced immune status with dendrite cell and lymphocyte-associated inflammatory activation as well as NK cell- and B cell-associated defense response aberrance. LJD played an inhibitory role in T cell activation, a process located downstream pathological cascade of psoriasis.

A review for natural polysaccharides with anti-pulmonary fibrosis properties, which may benefit to patients infected by 2019-nCoV.

Pulmonary fibrosis (PF) is a lung disease with highly heterogeneous and mortality rate, but its therapeutic options are now still limited. Corona virus disease 2019 (COVID-19) has been characterized by WHO as a pandemic, and the global number of confirmed COVID-19 cases has been more than 8.0 million. It is strongly supported for that PF should be one of the major complications in COVID-19 patients by the evidences of epidemiology, viral immunology and current clinical researches. The anti-PF properties of naturally occurring polysaccharides have attracted increasing attention in last two decades, but is still lack of a comprehensively understanding. In present review, the resources, structural features, anti-PF activities, and underlying mechanisms of these polysaccharides are summarized and analyzed, which was expected to provide a scientific evidence supporting the application of polysaccharides for preventing or treating PF in COVID-19 patients.

HIV-negative plasmablastic lymphoma: report of 8 cases and a comprehensive review of 394 published cases.

BACKGROUND: Human immunodeficiency virus (HIV)-negative plasmablastic lymphoma (PBL) is a rare entity of diffuse large B-cell lymphoma (DLBCL). The clinicopathological features of and optimal treatment for HIV-negative PBL remain largely unknown. METHODS: To gain insight into this distinct lymphoma, we summarized the clinicopathologic characteristics of 8 unpublished HIV-negative PBLs and performed a comprehensive review of 394 published cases. RESULTS: Of the 8 unpublished PBLs, the median patient age was 53.0 years. Four patients presented with stage IV disease. All 8 patients showed a plasma cell-like immunophenotype. Of the six patients who received anthracycline-based chemotherapy, including two who received bortezomib, three patients achieved a continuous complete response, two patients died due to disease progression, and one patient was lost to follow-up. The other two patients achieved continuous complete response after receiving chemotherapy combined with radiotherapy and surgery. Of the 402 patients, the majority were male, with a mean age of 58.0 years. EBV infection was detected in 55.7% of the patients. The median survival times of the patients who received CHOP or CHOP-like regimens and intensive regimens were not reached and 23.0 months, respectively, and the intensive regimen did not improve the survival outcome (P=0.981). Multivariate analysis showed that EBER remained the only independent factor affecting overall survival (OS). CONCLUSION: HIV-negative PBL is a distinct entity with a predilection for elderly and immunosuppressed individuals. Intensive chemotherapy had no apparent survival benefits over the CHOP regimen in terms of OS; the prognosis of this disease is poor with current chemotherapy methods, and treatment remains a challenge.

Airborne Bacteria Enriched PM2.5 Enhances the Inflammation in an Allergic Adolescent Mouse Model Induced by Ovalbumin.

Air pollution events frequently occur in China during the winter. Most investigations of pollution studies have focused on the physical and chemical properties of PM2.5. Many of these studies have indicated that PM2.5 exacerbates asthma or eosinophil inflammation. However, few studies have evaluated the relationship between bacterial loads in PM2.5, and especially pathogenic bacteria and childhood asthma. Airborne PM2.5 samples from heavily polluted air were collected in Hangzhou, China between December 2014 and January 2015. PM2.5 and ovalbumin (OVA) were intratracheally administered twice in 4-week intervals to induce the allergic pulmonary inflammation in adolescent C57/BL6 mice. PM2.5 exposure caused neutrophilic alveolitis and bronchitis. In the presence of OVA, the levels of the Th2 cytokines IL-4, IL-12, and IL-17 were significantly increased in bronchoalveolar lavage fluids (BALF) after PM2.5 exposure, while eosinophil infiltration and mucin secretion were also induced. In addition to adjuvant effects on OVA-induced allergic inflammation, PM2.5 exposure also led to the maturation of dendritic cells. These results suggest that PM2.5 exposure may aggravate lung eosinophilia and that PM2.5-bound microbial can exacerbate allergic and inflammatory lung diseases.

Characterization of coal-based fulvic acid and the construction of a fulvic acid molecular model.

Fulvic acid (FA) is important in modern agriculture, ecological restoration, life science, and medicine. The precise characterization of the composition and molecular structure of FA has become a key scientific issue in both basic and applied research. In this study, coal-based FA was separated by microwave-assisted oxygenation from lignite originating from Inner Mongolia in China. Through elemental analysis, infrared spectroscopy, nuclear magnetic resonance spectroscopy, classical quantitative titration experiments, and quantum chemistry combined with software analysis, the representative microscopic molecular structure of FA was determined. The results show that coal-based FA mainly contains three kinds of benzene ring substituents, ether bonds, hydrogen bonds, carbonyl groups, hydroxyl groups, carboxyl groups, phenolic hydroxyl groups, and semiquinonyl groups. The oxygen content is high, the carbon-to-oxygen ratio is less than 1, and the hydrogen-to-carbon ratio is 1.09. The ratio of aromatic carbon to total carbon is approximately 0.6, and benzene rings are connected to each other by an ether-oxygen bridge. The fat chain length of FA is approximately 0.47. FA has a small molecular structure with many acidic groups, primarily carboxyl groups and phenolic hydroxyl groups. The two-dimensional planar molecular structure of FA was established; the chemical formula is C38H32NO24, and the relative molecular mass is 886. The lowest-energy, structurally optimized three-dimensional characteristic ball-and-stick and stick models were also constructed. The calculated infrared spectrum of the molecular structure matches well with the experimental spectrum of FA, and the types and distributions of functional groups agree with the findings of previous studies. The quantum chemical data confirm that the proposed molecular structure is reasonable. The findings provide a scientific reference for applied research on FA in the future.